Uncontrolled cell proliferation leads to numerous disease conditions. Some of the most severe consequences of hyperproliferation lead to malignant tumors, of which many can be life threatening. Other consequences of increased cell proliferation lead to benign conditions that cause mild to severe discomfort or pain, often requiring surgical and/or pharmacological intervention.
Both synthetic and naturally occurring retinoids are generally recognized to be effective for the prevention, as well as the treatment of a wide range of hyperproliferative conditions for dermatological and non-dermatological applications. Retinoids are believed to represent a physiological, rather than a cytotoxic, approach to arresting, reversing, or regulating hyperproliferation of epithelial cells. The fundamental theory underlying retinoid efficacy is the ability of retinoids to enhance normal physiological mechanisms which protect the organism against hyperplastic conditions. However, the therapeutic use of retinoids is limited due to poor efficacy and/or undesirable side effects.
Retinoids increase the production and secretion of the peptide growth factor, transforming growth factor, type beta (TGF-.beta.) from human epidermal cells (Glick, et al., Cell Regulation, Vol. 1 (1989), pp. 87-97). This effect is important for certain therapeutic benefits of retinoids. TGF-.beta. is produced by normal and malignant cells and is known to have a non-cytotoxic inhibitory effect on epithelial cell proliferation. Hyperproliferation of epithelial cells may involve a reduction of TGF-.beta. levels in any given tissue compartment and/or a loss of sensitivity to target cells. Consequently, the induction of TGF-.beta. secretion is significant in the prevention and treatment of cancer and broadly related non-malignant hyperproliferative conditions.
It is an object of the subject invention to provide methods for treating hyperproliferative conditions in mammals.
It is a further object of the subject invention to provide methods for the treatment and prevention of hyperproliferative conditions which are more efficacious and have fewer side effects than retinoids.